Effects of Prostaglandins E₁ E₂ and F_2α on Contractility and cAMP and cGMP Contents in Lower Urinary Tract Smooth Muscle

Abstract

Prostaglandin (PG) E₁ E₂ and F_2α contracted smooth muscle strips from male adult rabbit urinary bladder. Contractile responses to each PG were significantly greater in urinary bladder body than in urinary bladder base. The magnitude of contractile response to each PG was F_2α > E₂ > E₁ in both of the bladder body and the bladder base. These contractions were almost completely eliminated by a calcium entry blocker, verapamil but not by atropine, phentolamine, propranolol or tetrodotoxin. PG E₁ and E₂ significantly relaxed the male rabbit urethral smooth muscle strips, whereas PG F_2α contracted the urethral smooth muscle strips. Cyclic adenosine monophosphate (cAMP) but not cyclic guanosine monophosphate (cGMP) increased significantly after administration of PG E₁ or E₂ in the urethral muscle strip. These results suggest that the regional differences in the magnitude of contractile responses to PG E₁, E₂ and F_2α between the bladder dome and the base and also suggest the contractile differences of PG E₁ and E₂ for the urinary bladder and the urethra; contractions for bladder and relaxations for urethra. These results also demonstrate that contractions induced by PG E₁, E₂ and F_2α in urinary bladder smooth muscles and by PG F_2α in urethral smooth muscles are mainly mediated by calcium influx and that relaxations induced by PG E₁ and E₂ in urethral smooth muscles are mediated by cAMP but not by cGMP.

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

“…PGE 1 , PGE 2 , and PGF 2␣ all contract detrusor muscle, but in the urethra, PGE 1 and PGE 2 cause relaxation, whereas PGF 2␣ produces contraction (Andersson, 1993). This pattern of effects has been demonstrated in animal (Persson and Andersson, 1976;Khanna et al, 1978;Gotoh et al, 1986;Morita et al, 1994;Pinna et al, 1996), as well as human urethral smooth muscle (Andersson et al, 1978a). In women receiving PGE 2 intravesically or intraurethrally, a decrease in the maximum urethral pressure and a reduction of the closure pressure were found (Andersson et al, 1978a;Schussler, 1990).…”

“…In women receiving PGE 2 intravesically or intraurethrally, a decrease in the maximum urethral pressure and a reduction of the closure pressure were found (Andersson et al, 1978a;Schussler, 1990). Morita et al (1994) showed that PGE 1 and PGE 2 significantly relaxed the male rabbit urethral smooth muscle strips, whereas PGF 2␣ caused contraction. In the strips, cAMP, but not cGMP, increased significantly after administration of PGE 1 or PGE 2 .…”

Phosphodiesterases (PDEs) and PDE inhibitors for treatment of LUTS

“…1 However, few investigations have addressed the cAMP-and cGMP-mediated signal transduction pathways and their key enzymes in the mammalian urethra. Morita et al 9,42 examined the effects of PGE 1, PGE 2, isoproterenol, and SNP on the contractile force and tissue content of cAMP and cGMP in the rabbit bladder and urethra. They concluded that these substances, mediated by both cGMP and cAMP, but mainly by cGMP, can induce relaxation of the urethra.…”

Changes in prostaglandin E2 in patients with idiopathic overactive bladder syndrome after botulinum toxin type A treatment: is there a clinical benefit?

“…But how far are local urinary levels of the inflammatory mediators relevant to the inflammatory process at all? In particular, anticholinergics and BoNT-A are acting by different receptor mediated signal transduction pathways affecting Ca ++ influx with impact on PGE2 release [29, 30]. The regulation and action of prostaglandins in the urinary bladder are still obscure.…”